Most people are aware that anti-cancer treatments often have negative side effects, but patients are willing to tolerate these side effects for the potential life-saving effects of the treatment. However, some patients treated with the anti-cancer drug 5-Fluorouracil (5-FU) will have fatal reactions typically caused by cardiotoxicity. A life-saving diagnostic test to identify cancer patients who may experience 5-FU toxicity has been developed by scientists at the National Cancer Institute (NCI). Thus, it is possible to avoid 5-FU toxicity by using this diagnostic screening test prior to the administration of 5-FU. 

The diagnostic test is based on screening for a mutation in the dihydropyrimidine dehydrogenase (DPD) gene. DPD is involved with the degradation of 5-FU, and it has been shown that patients exhibiting 5-FU toxicity have low DPD activity levels. In 1994, Dr. Frank Gonzalez and his colleague at NCI determined the molecular basis (a splicing mutation) for the DPD deficiency observed in patients with 5-FU toxicity and developed a method to detect the mutation. Since then, this discovery has been translated into multiple commercial products that are used to detect the mutation and allow healthcare providers to offer optimal anti-cancer treatment. 

5-FU is used for the treatment of multiple cancers, including breast and colon cancers. In the United States, approximately 275,000 cancer patients receive 5-FU annually. It is estimated that 3% of those patients develop some degree of toxic reaction. Patients suffering toxic reactions are difficult and expensive to treat further. Approximately 15% of those developing a toxic reaction will die as a result of exposure to 5-FU. More than 1,300 patients in the United States die each year as a result of 5-FU toxicity. These deaths are all potentially avoidable if patients are screened prior to the administration of 5-FU using the diagnostic test developed by NCI. 

This technology has been licensed nonexclusively to several licensees. The transfer of this technology through these nonexclusive licenses has enabled the wide dissemination of this test in the United States and Europe. As a result of these multiple licenses, many more people around the globe can forego being treated by a drug that may do more harm than good. The wide dissemination of this life-saving diagnostic test promotes the NIH mission of improving public health. 

Awardees

National Cancer Institute

• Dr. Frank Gonzalez

Universidad de Extremadura (Spain)

• Dr. Pedro Fernandez-Salguero